DESCRIPTION OF THE FOURTH CASE OF ACERULOPLASMINEMIA FOUND IN ITALY

Pathogenesis and molecular mechanisms of anderson–fabry disease and possible new molecular addressed therapeutic strategies

Anderson–Fabry disease (AFD) is a rare disease with an incidenceof approximately 1:117,000 male births. Lysosomal accumulation of globotriaosylceramide (Gb3) is the element characterizing Fabry disease due to a hereditary deficiency α-galactosidase A (GLA) enzyme. The accumulation of Gb3 causes lysosomal dysfunction that compromises cell signaling pathways. Deposition of sphingolipids occurs in the autonomic nervous system, dorsal root ganglia, kidney epithelial cells, vascular system cells, and myocardial cells, resulting in organ failure. This manuscript will review the molecular pathogenetic pathways involved in Anderson–Fabry disease and in its organ damage. Some studies reported that i…

Antiplatelet treatment in ischemic stroke treatment.

Antiplatelets represent a diverse group of agents that share the ability to reduce platelet activity through a variety of mechanisms. Antithrombotic agents are effective in the secondary prevention of ischemic strokes. Most strokes are caused by a sudden blockage of an artery in the brain (called an ischaemic stroke) that is usually due to a blood clot. Immediate treatment with antiplatelet drugs such as aspirin may prevent new clots from forming and hence improve recovery after stroke. Several studies have evaluated the role of one antiplatelet agent, aspirin, in reducing stroke severity. The International Stroke Trial (IST) of 20,000 patients with acute stroke from other countries. In thi…

A curious case of pancytopenia and fever in a patient with Erdheim–Chester disease

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Sodium thiosulfate not always resolves calciphylaxis: an ambiguous response

Calciphylaxis is a severe “vascular ossification–calcification,” associated with a very high mortality rate that involvesarterial wall, venular wall, and nerves resulting in ischemia and necrosis of skin, subcutaneous fat, visceral organs,and skeletal muscles. Sodium thiosulfate has recently been used as a novel treatment option for calciphylaxisbecause of its dual role as an antioxidant and a chelator. Multiple case reports demonstrated that such therapy hasresulted in pain relief and healing of skin ulceration. We report a case of calciphylaxis of large severity that had anambiguous response to sodium thiosulfate treatment (improvement of symptomatology and skin lesions, improve-ment of b…

Genetics and Gene Therapy of Anderson-Fabry Disease.

Fabry's disease is a genetic disorder of X-linked inheritance caused by mutations in the alpha galactosidase A gene resulting in deficiency of this lysosomal enzyme. The progressive accumulation of glycosphingolipids, caused by the inadequate enzymatic activity, is responsible of organ dysfunction and thus of clinical manifestations. In the presence of a high clinical suspicion, a careful physical examination and specific laboratory tests are required, finally diagnosis of Fabry's disease is confirmed by the demonstration of absence or reduced alpha-galactosidase A enzyme activity in hemizygous men and gene typing in heterozygous females; in fact the performance of enzymatic activity assay …

Molecular Mechanisms of Inflammasome in Ischemic Stroke Pathogenesis.

Ischemic stroke (also called cerebral ischemia) is one of the leading causes of death and severe disability worldwide. NLR inflammasomes play a crucial role in sensing cell damage in response to a harmful stimuli and modulating the inflammatory response, promoting the release of pro-inflammatory cytokines such as IL-18 and IL-1β following ischemic injury. Therefore, a neuroprotective effect is achieved by inhibiting the expression, assembly, and secretion of inflammasomes, thus limiting the extent of brain detriment and neurological sequelae. This review aims to illustrate the molecular characteristics, expression levels, and assembly of NLRP3 (nucleotide-binding oligomerization domain-like…

Inter-familial and intra-familial phenotypic variability in three Sicilian families with Anderson-Fabry disease.

// Antonino Tuttolomondo 1 , Irene Simonetta 1 , Giovanni Duro 2 , Rosaria Pecoraro 1 , Salvatore Miceli 1 , Paolo Colomba 2 , Carmela Zizzo 2 , Antonia Nucera 3, 4 , Mario Daidone 1 , Tiziana Di Chiara 1 , Rosario Scaglione 1 , Vittoriano Della Corte 1 , Francesca Corpora 1 , Danai Vogiatzis 1 and Antonio Pinto 1 1 U.O.C di Medicina Interna con Stroke Care, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S), University of Palermo, Palermo, Italy 2 CNR-IBIM: Institute of Biomedicine and Molecular Immunology “A. Monroy” Palermo, Palermo, Italy 3 Stroke Unit, Neurology, Saint Andrea Hospital, La Spezia, Italy 4 Department of Clinical Neurological Sciences, Western Univer…

Neurological complications of Anderson-Fabry disease

Characteristic clinical manifestations of AFD such as acroparesthesias, angiokeratoma, corneal opacity, hypo/ and anhidrosis, gastrointestinal symptoms, renal and cardiac dysfunctions can occur in male and female patients, although heterozygous females with AFD usually seems to be less severely affected. The most prominent CNS manifestations consist of cerebrovascular events such as transient ischaemic attacks (TIAs) and (recurrent) strokes . For the most part, CNS complications in AFD have been attributed to cerebral vasculopathy, including anatomical abnormalities. The natural history of Fabry patients includes transitory cerebral ischaemia and strokes, even in very young persons of both …

Novel alpha-galactosidase A mutation in a female with recurrent strokes.

Abstract Anderson–Fabry disease (AFD) is an X-linked inborn error of glycosphingolipid catabolism resulting from the deficient activity of the lysosomal exoglycohydrolase, a-galactosidase A. The complete genomic and cDNA sequences of the human alpha-galactosidase A gene have been determined and to date, several disease-causing alpha-galactosidase A mutations have been identified, including missense mutations, small deletions/insertions, splice mutations, and large gene rearrangements We report a case of a 56-year-old woman with recurrent cryptogenic strokes. Ophthalmological examination revealed whorled opacities of the cornea (cornea verticillata) and dilated tortuous conjunctival vessels.…

A family with various symptomatology suggestive of Anderson-Fabry disease and a genetic polymorphism of alpha galactosidase A gene.

Background: Anderson/Fabry disease expresses a wide range of clinical variability in patients that it is possible to explain referring to a genetic variability with numerous mutations described in the literature (more than 600). Methods: We report some clinical cases of some members of a Sicilian family to express phenotypical variability of this disease in subjects with the same genetic mutation. Results: The first case was a 59-year-old female. Brain MRI revealed right frontal periventricular white matter of likely vascular-degenerative origin. The proband's alpha galactosidase A activity was 3.7. nmol/mL/h. Molecular genetics revealed a polymorphism: - 10 C. >. T; IVS 2-76_80del5; IVS…

Effects of ACE-Inhibitors and Angiotensin Receptor Blockers on Inflammation

The role of inflammation in cardiovascular disease and in hypertensive disease above all, is complex. Several studies confirm that activation of renin-angiotensin-aldosterone system (RAAS), through increase in the production of angiotensin II (Ang II), is closely related to local vascular inflammation. Over the BP lowering effects of anti-hypertensive treatments, several ancillary effects for every class may be found, distinguishing the various drugs from one another. Given the pro-inflammatory effects of Ang II and aldosterone, agents that interfere with the components of RAAS, such as ACE inhibitors, Angiotensin Receptor Blockers (ARBs), and mineralocorticoid receptor antagonists (spirono…

42 PROGNOSIS OF ACUTE ISCHEMIC STROKE RELATED WITH CARDIOVASCULAR DRUGS TREATMENT DURING HOSPITAL STAY

Drug Prescription and Delirium in Older Inpatients: Results From the Nationwide Multicenter Italian Delirium Day 2015-2016

Objective This study aimed to evaluate the association between polypharmacy and delirium, the association of specific drug categories with delirium, and the differences in drug-delirium association between medical and surgical units and according to dementia diagnosis. Methods Data were collected during 2 waves of Delirium Day, a multicenter delirium prevalence study including patients (aged 65 years or older) admitted to acute and long-term care wards in Italy (2015-2016); in this study, only patients enrolled in acute hospital wards were selected (n = 4,133). Delirium was assessed according to score on the 4 "A's" Test. Prescriptions were classified by main drug categories; polypharmacy w…

"Delirium Day": a nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods This is a point prevalence study (called “Delirium Day”) including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium wa…

The supraventricular tachycardias: Proposal of a diagnostic algorithm for the narrow complex tachycardias

AbstractThe narrow complex tachycardias (NCTs) are defined by the presence in a 12-lead electrocardiogram (ECG) of a QRS complex duration less than 120ms and a heart rate greater than 100 beats per minute; those are typically of supraventricular origin, although rarely narrow complex ventricular tachycardias have been reported in the literature.As some studies document, to diagnose correctly the NCTs is an arduous exercise because sometimes those have similar presentation on the ECG. In this paper, we have reviewed the physiopathological, clinical, and ECG findings of all known supraventricular tachycardias and, in order to reduce the possible diagnostic errors on the ECG, we have proposed …

A case of infective colitis due to Yersinia enterocolitica complicated by microliver abscesses mimicking multiple liver occult metastases: a case report

Abstract Background We report an unusual case of infective colitis by Yersinia enterocolitica complicated by microliver abscesses mimicking multiple liver metastases in a 79 yr old female without any risk factors for bacteriaemia by this pathogen. Case presentation The patient was admitted to the Internal Medicine with Stroke Care ward of University Policlinico “P. Giaccone” in Palermo because of the appearance of diarrhoea. After the antimicrobial treatment for infective colitis, the clinicians observed a persistently increased white blood cells (WBC) count and multiple hepatic lesions; after having excluded any neoplastic disease and inflammatory bowel disease (IBD), blood cultures positi…

Recurrent venous thromboembolism complicated by heparin-induced thrombocytopenia as a first manifestation of an occult cancer: a case report.

Heparin-Induced Trombocytopenia (HIT) is a serious and potentially fatal complication of patients on heparins. Its management is difficult and it can be more complicated in patients with cancer because of the hemorrhagic risk carried out by direct inhibitor of thrombin, the currently approved drug for HIT. At present, it is not clear whether cancer patients also have an increased risk of HIT. We describe the case of a patient with occult cancer at the moment of the index venous thrombosis, who developed Deep Vein Thrombosis (DVT) and concomitant HIT with thrombotic complications (recurrent contralateral venous thrombosis). The management of HIT was efficaciously based on the combined use o…

Anderson-Fabry Disease: A Multiorgan Disease

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by a deficiency of the enzyme α-galactosidase A . FD causes glycolipids, such as globotriaosylceramide (Gb3), to accumulate in the vascular endothelium of several organs (fig.2), including the skin, kidneys, nervous system, and heart, thereby triggering inflammation and fibrosis . These processes generally result in organ dysfunction, which is usually the first clinical evidence of FD. Patients with classic FD have various symptoms, eg, acroparesthesias, hypohidrosis, angiokeratomas, corneal opacities, cerebrovascular lesions, cardiac disorders, andrenal dysfunction.However, evolving knowledge about the natural course o…

Treatment of Anderson-Fabry Disease

Fabry disease is an X-linked disorder of glycosphingolipid metabolism that results in progressive accumulation of neutral glycosphingolipids, predominantly globotriaosylsphingosine (Gb3) in lysosomes, as well as other cellular compartments of several tissues, causing multi-organ manifestations (acroparesthesias, hypohidrosis, angiokeratomas, signs and symptoms of cardiac, renal, cerebrovascular involvement). Pathogenic mutations lead to a deficiency of the lysosomal enzyme alpha-galactosidase A (GLA). In the presence of high clinical suspicion, a careful physical examination and specific laboratory tests are required. Finally, the diagnosis of Fabry’s disease is confirmed by the demonstrat…